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pronounced curvature in their tubular segments than the cerebral hemispheres and diencephalon, the midbrain
those in suspension culture. The study revealed that retains a relatively primitive structure, and the hindbrain
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mechanical and soluble signals generated by 3D packaging differentiates into the cerebellum, pons, and medulla
in alginate gel modulate nephron patterns and morphology oblongata. Each brain region starts to develop preliminary
of renal organoids, highlighting the importance of the functional areas. During embryonic development
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3D mechanical microenvironment in renal regenerative and early post-natal periods, many cortical neurons are
medicine and that the degree of cell-induced hydrogel generated. In infancy and childhood, synaptic connections
deformation widely modulates epithelial morphogenesis between neurons are established, leading to the proliferation
during 3D organoid culture. of neural networks. Subsequently, synaptic plasticity
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Strategies aimed at regulating cell-ECM interactions ensures the removal of unnecessary synapses through
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during organoid development have remained largely pruning, which warrants precision in brain function. In
underexplored. Garreta et al. used renal ECM-derived addition, there are significant differences between human
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hydrogels transplanted into the chicken chorioallantoic brain development and rodent models, including variations
membrane to demonstrate their angiogenic potential in developmental processes, brain volume, and genotype. In
(Figure 5B). The isolation and aggregation of posterior humans, the ventricular subependyma (SVZ) is divided by
the inner fiber layer into the inner SVZ and the outer SVZ
intermediate mesoderm cells into spheres and the addition
of dECM hydrogels to the culture medium every other (OSVZ). However, the OSVZ is not present in commonly
day effectively induced a significant number of renal used rodent models. This discrepancy leads to insufficient
vesicles by day 11, with positive expression of intermediate model accuracy and experimental bias in present research,
24
mesoderm markers (PAX2, WT1, and LHX1). By day highlighting the need for brain organoid studies.
20 of differentiation, the cells spontaneously patterned Isik et al. developed a biologically active hydrogel with
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and segmented into typical nephron-like components, tunable stiffness to cultivate and induce cerebral organoids
including renal tubules (ECAD ), glomeruli (NEPHRIN ), (COs). The hydrogel was constructed from peptide
+
+
+
and endothelial cells (CD31 ) (Figure 5C). This indicates amphiphiles (PAs) and HA. PAs offer well-defined chemical
that dECM hydrogels enhance cell-ECM interactions, structures, tunable bioactivity, and nanofibrillar ECM-
promoting the differentiation and angiogenesis of renal like architectures, making them an ideal support scaffold
organoids (Figure 5D), thereby solving the problem of for organoid growth. Hydrogels with adjustable stiffness
regulating the interaction between cells and ECM during were successfully created by crosslinking PAs bearing the
organogenesis. 123 bioactive Ile-Lys-Val-Ala-Val peptide sequence with HA
functionalized with tyramine groups. By employing multi-
The complexity of the structure and function of kidneys
cannot be fully replicated by existing technologies, limiting omics approaches, including transcriptomics, proteomics,
their application in disease modeling and regenerative and metabolomics, the study found that COs grown in
medicine. Nerger et al. have demonstrated the significance these hydrogels exhibited morphological and biomolecular
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features similar to those grown in Matrigel. This hydrogel
of the 3D mechanical microenvironment in kidney organ material shows promise as a safe synthetic ECM for CO
development, while Garreta et al. have showcased the induction and growth, providing a defined alternative to
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potential of ECM in enhancing the vascularization of
kidney organs. However, strategies to modulate cell-ECM animal-derived matrices for CO-based basic and clinical
studies. Cho et al. promoted the structural and
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interactions require further exploration. Future research functional maturation of human brain-like organs using
should focus on developing more effective methods to microfluidic devices and the brain ECM (BEM). They
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regulate these critical factors to achieve kidney organ developed a microfluidic device that facilitates dynamic
engineering that more closely mimics the organ.
fluid flow and introduces BEM into organoids (Figure 6A).
4.5. Nervous system They found that using microfluidic devices and BEM
significantly improved the structure and function of brain
4.5.1. Brain organoids. Brain organoids using microfluidic devices
During early embryonic development, the ectoderm forms and BEM have better cell survival rates and proliferation
the neural plate, which subsequently folds to create the than traditional culture methods. The microfluidic culture
neural tube, the pre-cursor of the central nervous system. improved oxygen supply within the brain organoids
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By the 4 week, the neural tube begins to close, forming promoting the increase of nerve cell population and
th
the initial brain and the extending spinal cord structure. thickening of neuroepithelium. Moreover, compared with
Around the 5 week, the anterior end of the neural tube BEM-cultured organoids, those grown in Matrigel exhibited
th
expands into three primary brain vesicles: the forebrain, smoother and smaller morphologies. This suggests that
midbrain, and hindbrain. The forebrain differentiates into BEM promotes volume expansion, structural maturation,

Volume 1 Issue 2 (2025) 15 doi: 10.36922/or.8262